Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes

Eli Rothenberg, Jill M. Grimme, Maria Spies, Taekjip Ha

Research output: Contribution to journalArticle

Abstract

The Rad52 protein has critical functions in distinct pathways of the homology-directed DNA repair, one of which is to promote the annealing of complementary strands of DNA. Both yeast and human Rad52 proteins organize into ring-shaped oligomers with the predominant form being a heptamer. Despite the wealth of information obtained in previous investigations, how Rad52 mediates homology search and annealing remains unclear. Here, we developed single-molecule fluorescence resonance energy transfer approaches to probe hRad52-mediated DNA annealing events in real time. We found that annealing proceeds in successive steps involving rearrangements of the ssDNA-hRad52 complex. Moreover, after initial pairing, further search for extended homology occurs without dissociation. This search process is driven by an interaction between 2 overlapping nucleoprotein complexes. In light of these observations we propose a model for hRad52-mediated DNA annealing where ssDNA release and dsDNA zippering are coordinated through successive rearrangement of overlapping nucleoprotein complexes.

Original languageEnglish (US)
Pages (from-to)20274-20279
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number51
DOIs
StatePublished - Dec 23 2008
Externally publishedYes

Keywords

  • DNA recombination
  • DNA repair
  • FRET
  • Fluorescence microscopy
  • Single-molecule

ASJC Scopus subject areas

  • General

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